Resolution of 3-benzoylthio-2-methyl-propanoic acid with (+)-dehydroabietylamine

Abstract

Disclosed herein is a process for the preparation of optically active compounds of the formula: ##STR1## in which R is a lower alkyl, lower alkoxy, benzyloxy, phenyl, o-nitrophenyl, p-nitrophenyl, or p-tolyl group, or salts or esters thereof, which process comprises the following steps: (a) starting with a racemic mixture of the compound of Formula I in which R is phenyl, namely, (+)-3-benzoylthio-2-methylpropanoic acid; (b) adding thereto 0.40-0.60 moles of (+)-dehydroabietylamine per mole of (+)-3-benzoylthio-2-methyl-propanoic acid as the resolving agent, in the presence of an aliphatic carboxylic acid lower alkyl ester as the resolution solvent; (c) crystallizing out and isolating the (-)-3-benzoylthio-2-methylpropanoic acid, (+)-dehydroabietylamine salt, which is dextrorotary; (d) if necessary, recrystallizing said dextrorotary salt to further purify it; (e) hydrolyzing the resulting dextrorotary salt with a base to separate the (+)-dehydroabietylamine resolving agent from the (-)-3-benzoylthio-2-methyl propanoate; (f) hydrolyzing the (-)-3-benzoylthio-2-methyl-propanoate with an acid to form the acid thereof; (g) optionally, converting the phenyl group of the resulting (-)-3-benzoylthio-2-methyl-propanoic acid to one of the other R groups of Formula I.

We claim: 
     
       1. A process for the resolution of (±)-3-benzoylthio-2-methyl-propanoic acid to obtain the (-)isomer thereof, which process comprises the following steps: (a) starting with a racemic mixture of said (±)-3-benzoylthio-2-methyl-propanoic acid;   (b) adding thereto 0.40-0.60 moles of (+)-dehydroabietylamine per mole of (±)-3-benzoylthio-2-methyl-propanoic acid as the resolving agent, in the presence of an aliphatic carboxylic acid lower alkyl ester, the acid and alcohol portions of which are lower alkyl groups of 1 to 4 carbon atoms, as the resolution solvent;   (c) crystallizing out and isolating the (-)-3-benzoylthio-2-methyl-propanoic acid, (+)-dehydroabietylamine salt, which is dextrorotary;   (d) hydrolyzing the resulting dextrorotary salt from (c) with a base to separate the (+)-dehydroabietylamine resolving agent from the (-)-3-benzoylthio-2-methyl propanoate; and   (e) hydrolyzing the (-)-3-benzoylthio-2-methyl-propanoate with an acid to form the acid thereof.   
     
     
       2. A process according to claim 1 wherein the range of moles of (+)-dehydroabietylamine is 0.45-0.60. 
     
     
       3. A process according to claim 1 wherein the aliphatic carboxylic acid lower alkyl ester is selected from ethyl acetate or methyl acetate.